Structural and functional characterization of podocyte antigens in autoantibody-mediated glomerulonephritis (B02)

• Subject Area: Nephrology
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264599542

In this project we will pursue the following aims: 1) Characterization of the newly discovered anti-nephrin autoantibodies in MCD including clinical correlations, analysis of immunodominant epitope-containing regions and epitope-specific antigen-antibody interaction. 2) Investigation of the structure-function relationship between epitope-dependent antibody binding, antibody-mediated disturbances in nephrin signaling and therapeutic blocking of antibody binding. 3) High-resolution structural analysis of podocyte antigens including antibody-binding regions of THSD7A and nephrin by means of x-ray crystallography and cryo-electron microscopy. Taken together, the analysis of high-resolution antigen structure, antigen-antibody interaction and epitope-dependent signaling programs will lead to a deeper molecular understanding of autoantibody-mediated glomerular diseases and the role of the SD as a target of autoimmunity.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1192: Immune-Mediated Glomerular Diseases - Basic Concepts and Clinical Implications -
• Applicant Institution: Universität Hamburg
• Project Heads: Dr. Felicitas E. Hengel; Professor Dr. Tobias B. Huber, since 1/2020; Professor Matthias Wilmanns, Ph.D., since 1/2020